Regional specificity of MRI contrast parameter changes in normal ageing revealed by voxel-based quantification (VBQ)

Abstract

Normal ageing is associated with characteristic changes in brain microstructure. Although in vivo neuroimaging captures spatial and temporal patterns of age-related changes of anatomy at the macroscopic scale, our knowledge of the underlying (patho)physiological processes at cellular and molecular levels is still limited. The aim of this study is to explore brain tissue properties in normal ageing using quantitative magnetic resonance imaging (MRI) alongside conventional morphological assessment. Using a whole-brain approach in a cohort of 26 adults, aged 18–85 years, we performed voxel-based morphometric (VBM) analysis and voxel-based quantification (VBQ) of diffusion tensor, magnetization transfer (MT), R1, and R2* relaxation parameters. We found age-related reductions in cortical and subcortical grey matter volume paralleled by changes in fractional anisotropy (FA), mean diffusivity (MD), MT and R2*. The latter were regionally specific depending on their differential sensitivity to microscopic tissue properties. VBQ of white matter revealed distinct anatomical patterns of age-related change in microstructure. Widespread and profound reduction in MT contrasted with local FA decreases paralleled by MD increases. R1 reductions and R2* increases were observed to a smaller extent in overlapping occipito-parietal white matter regions. We interpret our findings, based on current biophysical models, as a fingerprint of age-dependent brain atrophy and underlying microstructural changes in myelin, iron deposits and water. The VBQ approach we present allows for systematic unbiased exploration of the interaction between imaging parameters and extends current methods for detection of neurodegenerative processes in the brain. The demonstrated parameter-specific distribution patterns offer insights into age-related brain structure changes in vivo and provide essential baseline data for studying disease against a background of healthy ageing.

High-resolution characterisation of the aging brain using simultaneous quantitative susceptibility mapping (QSM) and R2* measurements at 7 T

“…The high R2* values for the GP (independent of age) in contrast to thalamus, caudate and putamen are consistent with previous in vivo R2* reports and post-mortem correlations with iron concentration (Gelman et al, 1999;Langkammer et al, 2010;Péran et al, 2009;Yao et al, 2009). Furthermore, agerelated increase in R2* have been reported previously in the GP in some studies (Callaghan et al, 2014;Draganski et al, 2011). On the other hand, the lack of a significant age-related difference in the GP with QSM in the present study is consistent with previous post-mortem evidence (Hallgren and Sourander, 1958), and confirmed in vivo (Li et al, 2014), that iron deposition in the GP increases rapidly from birth until the second decade of life but thereafter plateaus.…”

Lost and Forgotten? Orientation Versus Memory in Alzheimer's Disease and Frontotemporal Dementia

“…31], or not [e.g. 32]. We think our current approach with a cluster extent threshold of 20 contiguous voxels is on the conservative side of studies investigating subcortical atrophy correlates of cognitive dysfunction.…”

Tracking trauma-induced structural and functional changes above the level of spinal cord injury

“…This is because the degree of myelination, iron content and neuronal microstructure are reflected in MR relaxation times, magnetization transfer and diffusion-weighted images which can be measured at high resolution [14][15][16]. These novel quantitative MR methods include multiparametric mapping [17][18][19][20][21] and diffusion tensor imaging [22] next to volumetric measures (i.e. voxel-based morphometry [23]) and voxel-based cortical thickness [24].…”